Fear-enhancing effects of septal oxytocin receptors

Although oxytocin is generally thought to exert anxiolytic, prosocial and antistress effects, reports of anxiogenic effects in humans have recently emerged. Here the authors show that oxytocin receptors in the lateral septum mediate the stress-induced enhancement of fear conditioning in mice in a process involving MAPK-ERK signaling. The nonapeptide oxytocin is considered beneficial to mental health due to its anxiolytic, prosocial and antistress effects, but evidence for anxiogenic actions of oxytocin in humans has recently emerged. Using region-specific manipulations of the mouse oxytocin receptor (Oxtr) gene (Oxtr), we identified the lateral septum as the brain region mediating fear-enhancing effects of Oxtr. These effects emerge after social defeat and require Oxtr specifically coupled to the extracellular signal–regulated protein kinase pathway.